Diet is the main supplier of amino acids (AA), and in recent years their role in the modulation of cellular signaling and metabolic processes has been studied. Diets supplemented with glutamate or tryptophan enhance lifespan of worms1, and the imbalance in GABA and tryptophan metabolism modulates the development of neurodegenerative diseases2,3. We previously observed that in the
mec-4d model of neurodegeneration in C. elegans, the rate of neuronal death depends on the type of bacterial diet. Feeding worms with Escherichia coli B strain OP50 does not prevent neuronal death at 72 hours post hatching (<2% wild type (wt) AVM morphology), instead Comamonas aquatica, Comamonas testosteroni and Bacillus megaterium diets provide modest neuroprotection levels (10-20%). Surprisingly, Escherichia coli K12 strain HT115 induced almost 45% of wt AVM neurons, which doubles the neuroprotective effect described with other diets4. To decipher which metabolic pathways were involved in neuroprotection, E. coli OP50 and HT115 were selected for transcriptomic, genetic and biochemical comparison as diets for
mec-4d worms. Transcriptomic approaches discovered differential expressed genes between both bacteria. The glyceraldehyde 3-phosphate dehydrogenase (gap), involved in the glycolysis pathway, and glutamate decarboxylase (gad), required for GABA production, are unique and highly expressed genes in E. coli HT115. gadA mutant HT115 bacterial diet showed significant differences in neuroprotection in
mec-4d worms, highlighting the the relevance of a GAD product. We are currently investigating the role of GABA in neuroprotection by supplementation of E. coli OP50. Additionally, we assessed the neuroprotective role of other molecules. Lipids of the HT115 strain were separated from the polar molecules, and the fractions were used for diet supplementation. Worms fed with the polar fraction showed 25% wt AVM morphology6. The described approaches will provide a robust evidence to describe the responsible AA and metabolites in neuroprotection, and the synergistic and synchronized mechanisms from nutrients signaling7. This study has potential relevance in understanding the bacterial and microbiome contribution in the modulation of neurodegenerative disease8.